Table 3.

Summary of important uterine tissue based protein biomarker candidates for EC detection.

Potential Biomarker	Gene Names	Summary of Evidence	Proteomic Techniques Used	Known Biochemical Function	Limitations	Panels
Chaperonin 10 (CPN 10)	HSPE1	Consistent Upregulated in EC tissues [89,92,94,95,96,103]	iTRAQ and cleavable isotope coded affinity tags (ciCAT) labelled LC-Tandem MS SELDI QTOF MSI	Chaperones involved in normal protein folding, cell signalling and maintenance of the conformation of transduction complexes	Heat-shock proteins are elevated in many other conditions.	CPN 10, PK and SERPINA1 had SEN, SPE and PPV of 0.95.
Calcyphosine (CAPS)	CAPS	Limited Upregulated in EC tissues [80,81,104].	2 DE Electrophoresis+MS Immunobloting immunohistochemistry	A phosphorylated substrate for cAMP-dependent protein kinase cross-signalling regulating proliferation and differentiation	Limited evidence	None
Pyruvate Kinase (PK)	PKM	Accumulating evidence Upregulated in EC tissues [89,93,96,104]	iTRAQ and ciCAT labelled LC-Tandem MS	Regulatory function in the glycolytic pathway	Non-specific, elevated in other malignant and metabolic conditions.	CPN10, PKM2, SERPINA1 had SEN 0.85, SPE 0.93, PV 0.90. [93]
Cyclophilin A (CYP A)	PPIA	Limited evidence Upregulated in EC by up to 27.23 fold [80,81]	2 DE Electrophoresis+MS Immunobloting immunohistochemistry	Protein folding and immune regulation. Exogenous CYPA may enhance cancer growth via interaction with CD147 and activation of ERK1/2 and MAPK pathways.	Upregulated in lung, pancreatic, hepatocellular and buccal squamous cell carcinomas.	None
Calgizzarin (S-100A11)	S-100A11	Limited evidence Upregulated in EC [89,103]	iTRAQ and ciCAT labelled LC-Tandem MS	Calcium binding protein which has roles in cell growth, apoptosis and low grade inflammation.	Non-specific.	None
Epidermal fatty acid binding protein (EFBP)	FABP5	Limited evidence E-FABP was upregulated by up to 6.56 fold in EC cases compared to controls [80,81].	2 DE Electrophoresis+MS Immunobloting immunohistochemistry	Fatty-acid binding protein involved in cellular signalling and influences gene expression, growth regulation and cell differentiation.	Up-regulated in oesophageal squamous cell cancer and down-regulated in less differentiated bladder cancer	None
Calgranulin A (S100A8)	S100A8	Limited evidence Upregulated in EC [94,103]	MALDI-TOF-MS SELDI-QTOF MSI	S-100 calcium binding protein expressed in multiple cell types. Act as calcium sensors and modulate inflammation.	Limited evidence, non-specific.	None
Other heat-shock proteins HSP27 HSP47	HSPB1 SERPINH1	Limited evidence Upregulated in EC tissues vs. controls [88,105]. Downregulated in EC [81,104]	2 DE Electrophoresis MALDI Q-TOF MS/MS	Protein folding, cell signalling and maintenance of the conformation of transduction complexes, cell proliferation and differentiation.	Non-specific, limited evidence.	None
Prohibitin (PHB)	PHB	Limited evidence Upregulated in EC tissues vs. Controls [88,106].	2 DE Electrophoresis LC–MS/MS	Inhibits DNA synthesis and regulates proliferation.	Limited evidence, few studies.	None
Transgelin (TAGLN)	TAGLN	Limited evidence Downregulated in EC [89,96]	iTRAQ and ciCAT labelled LC–Tandem MS	Involved in actin cross linking and protein gelling. Found in many fibroblasts and smooth muscle.	Limited evidence, few studies.	None
Phosphoglycerate kinase (PGK1)	PGK1	Limited evidence Upregulated in EC [88,107]	2 DE Electrophoresis + MS Immunohistochemistry	Regulatory enzyme in the glycolytic pathway.	Limited evidence, non-specific	None
Creatine kinase B	CKB	Limited evidence Downregulated in EC [89,96,104]	iTRAQ and ciCAT labelled LC–Tandem MS	Mainly expressed in brain and smooth muscles including vascular and uterine. Major role in energy transduction.	Limited evidence, non-specific	None
Serotransferrin precursor/Transferrin	TF	Limited evidence Upregulated in EC [88] Downregulated in EC [81,104].	2 DE Electrophoresis MALDI Q–TOF–MS/MS	Iron-binding plasma protein.	Limited evidence	None
Heterogeneous nuclear ribonucleoproteins (A2/B1,D0)	HNPRNPA1	Limited evidence Upregulated in EC [88,89].	iTRAQ and ciCAT labelled LC-Tandem MS 2 DE Electrophoresis	Protein complexes of RNA important in cell-cycle processes and DNA damage.	Limited evidence	None
Macrophage migratory inhibitory factor (MIF)	MIF	Limited evidence Upregulated in EC [89,96].	iTRAQ and ciCAT labelled LC–Tandem MS	Important regulator of the cell-mediated immunity and inflammation.	Limited evidence	None
Polymeric immunoglobulin receptor precursor (PIGR)	PIGR	Limited evidence Upregulated in EC vs. Controls [89,96].	iTRAQ and ciCAT labelled LC–Tandem MS	A receptor that binds polymeric IgA and IgM on basolateral surface of epithelial cells. Important in signalling and immunoglobulin transcytosis.	Limited evidence	None
Alpha-1-antitypsin precursor (AIAT)	SERPINA1	Limited evidence Down regulated in EC tissues [89,96].	iTRAQ and ciCAT labelled LC–Tandem MS	A serine protease inhibitor, inhibits enzymes such as trypsin	Limited evidence	None
Capping Actin Protein, Gelsolin Like (CAPG)	CAPG	Limited evidence Upregulated in EC tissues [104,108]. Downregulated in EC [81]	2 DE Electrophoresis + LC–MS/MS	Actin-based motility in non-muscle cells.	Limited and inconsistent evidence	None
Protein Deglycase (DJ-1)	PARK7	Limited evidence Upregulated in EC [108]	2 DE Electrophoresis + LC–MS/MS	Redox-sensitive chaperone and sensor for oxidative stress.	Limited evidence	None
Annexin-1,2 (ANXA 1,2)	ANXA1, ANXA2	Limited evidence Upregulated in EC [104,106,108]	2 DE Electrophoresis +LC–MS/MS Western blotting Tissue microarray	Bind to cellular membranes in a calcium-dependent manner, mimic glucocorticoid function and exhibits anti-inflammatory properties.	Limited evidence	None
Peroxiredoxin-1,4 (PRD-X1,X4)	PRDX1-4	Limited evidence Upregulated in EC [81,106]	LC–MS/MS Western blotting Tissue microarray	Scavenging of peroxides, protection from oxidative stress-induced apoptosis.	Limited evidence	None
Costars family protein ABRACL	ABRACL	Limited evidence Upregulated in EC [101]	2 DE Electrophoresis LC–MS/MS Western blotting	ABRACL is an 82 amino acid protein that regulates actin cytoskeleton dynamics and motility.	Limited evidence	None
Phosphoglycerate mutase 2 (PGAM2)	PGAM2	Limited evidence Upregulated in EC [101]	2 DE Electrophoresis LC–MS/MS Western blotting	Glycolytic enzyme modulating NADPH homeostasis, impacting cell proliferation and tumour growth.	Limited evidence	None
Glutathione synthetase (GSS)	GSS	Limited evidence Upregulated in EC [101]	2 DE Electrophoresis LC–MS/MS Western blotting	Cellular homeostasis and anti-oxidant properties.	Limited evidence	None
Desmin (Des)	DES	Limited evidence Downregulated in EC [81,105].	DIGE MALDI–TOF	Protein marker for muscle tissue	Limited evidence	None
Alpha enolase (ENO1)	ENO1	Limited evidence Upregulated in EC 220 fold [100,101,106]	2 DE Electrophoresis LC–MS/MS Western blotting	Glycolytic enzyme. Regulates the PI3K/AKT signalling pathway and induces tumorigenesis by activating plasminogen.	Limited evidence	None
Superoxide dismutase (SOD1&2)	SOD1 SOD2	Limited evidence SOD2 Upregulated in EC 5 fold [101]. SOD1 downregulated in EC [105]	2 DE Electrophoresis LC–MS/MS Western blotting	Has anti-apoptotic effects against oxidative stress, ionizing radiation, and inflammatory cytokines.	Limited evidence	None
Fibrinogen beta chain (FBG)	FBG	Limited evidence Upregulated in EC up to 400 fold [101].	2 DE Electrophoresis LC–MS/MS Western blotting	Blood-based glycoprotein	Limited evidence	None
Anterior Gradient 2 protein	AGR2	Limited evidence Upregulated in EC [81,104]	2 DE Electrophoresis MALDI Q–TOF MS/MS	A protein disulphide isomerase involved in protein folding and implicated in various cancers.	Limited evidence	None
Clusterin (CLU)	CLU	Limited evidence Upregulated in EC [96]	LC + Tandem MS/MS	Chaperone with anti-apoptotic properties.	Limited evidence	None